Intro Puzzles
Here you can see the original instructions of the intro puzzles. Translations: Deutsch | Svenska Tip : read carefully the texts, press on button "tell me more", reset the puzzle after a few try and redo. Sidechains Level 1-1: One Small Clash This is a protein. We need your help to fold it into the right shape! You can drag SIDECHAINS with the mouse. Get rid of the clash by clicking and dragging one of the sidechains away from the other. Level 1-2: Swing It Around Swing It Around 1.png Swing It Around 2.png You can't see the sidechains from this angle! Click and drag on the white background to''' rotate the view'. You can also move or zoom by holding ctrl or shift while you drag. Watch your score! It tells you how well the protein is folded. '''Level 1-3 : Shake' You've earned the SHAKE tool! You can use shake to fix clashes for you! When you think SHAKE has done a good enough job, you can press it again to Stop. Backbone packing Level 2-1: When Backbones Collide This is the BACKBONE of the protein. Sometimes the backbone is too close together. Click and drag the backbone to pull it appart! You can always Undo. Shake will adjust the sidechains for you." Level 2-2: Close the Gap Ot her times the backbone is too far apart. VOIDS are an indicator that there is empty space that needs to be filled. Try getting rid of some of the voids by dragging the backbone together! Remember to use SHAKE to get rid of the clashes! Oops, the helices are too far apart. Want to reset?" Level 2-3: Wiggle You now have access to a VERY powerful tool: the WIGGLE tool! Just like SHAKE tries to take care of sidechains, WIGGLE tries to let Foldit improve the backbone. WIGGLE gets stuck if it cannot increase the score. Click this button again to stop the tool. Hydrogen Bonding Level 3-1: Sheets Together Its time to learn about the best things for improving your score in Foldit - Hydrogen bonds! Try pressing Wiggle. Those blue and white bands are Hydrogen Bonds. They form when these zig-zaggy sheets line up together like this. Level 3-2: Lonely Sheets Time to matc h up some sheets! Wiggle doesn't always work by itself. You can connect these sheets with [[Rubber Bands|'RUBBER BANDS']] . Hold shift and drag from one to the other. Try it with this sheet! Hold shift and drag. Rubber Bands pull together when you Wiggle. Don't worry about individual sidechains. Try connecting the sheets with a Rubber Band. tip : put rubber bands between to two little sheets, wiggle, remove bands, shake and wiggle Level 3-3: Sheets and Ladders Thre e sheets have been torn apart! Rubber Bands are free! Make as many as you want. You can move the view around and drag the background. When you're close, you can remove the bands and Wiggle again. tip : put a rubber band at each end of the sheet with the end of the sheet above, wiggle, remove the bands, shake and wiggle. The step ladder are the sheets and the side the bands Le Foldit 1297974789.png Foldit 1297974837.png vel 3-4: Lock and Lower One of the sheets is out of place! Sheets like to be alongside each other. Remember, hydrogen bonds are great for your score. You can Freeze the sheets already in place. Hold shift and double click. tip ; one sheet is over the row, freeze the 2 sheets on each side of it, double click on them, put the sheet between this two, rotate to see if the protein is flat, shake and wiggle, Level 3-5: rebuild You might have guessed by now, but''' color''' is used to show how well part of the protein is folded. This loop appears to be a problem. You can deal with problematic segments by using the [[Rebuild|'REBUILD ']] tool. Rebuild tests out different shapes for the protein. Right click (for windows) on the backbone to start a Rebuild. You can stop when Rebuild finds the shape you want. Shake and Wiggle will take care of clashes. This looks like a good shape! Try a Shake and Wiggle to clean it up. You can Wiggle a single section. Right click and choose Wiggle Hydrophobics and Hydrophilics Level 4-1: Hide the Hydrophobics Orange sidechains are HYDROPHOBIC . They want to be buried inside the protein. These bubbles are called EXPOSEDS.' EXPOSEDS' may appear on unburied hydrophobics! (yellow ball moving). Blue 'sidechains need plenty of space. They should point outward. Orange sidechains should be kept surrounded. Hide it in the empty space in the protein's interior and move the blue hydrophilic away outside. Your score measures not only clashes, but also how well hydrophobics are hidden. ''tip : move the orange sidechain in the center. '''Level 4-2: Turn It Down Sometimes you need to rotate to bury the hydrophobics. You can rotate with the TWEAK tool. Right click the helix to find it. Click and hold the purple arrows to rotate. Click stop to finish the Tweak. The helix has turned and exposed a hydrophobic! Level 4-3: Flippin' Sheets One of these sheets has unburied hydrophobics. You can easily flip a sheet with Tweak. The straight (purple) arrows turn the sheet 180 degrees and shift it to maintain hydrogen bonds. Look for the sheet with the exposed hydrophobics, and click the new straight arrows on the Tweak tool to shift and flip it. You're almost there! Try a Wiggle to finish up. LennStar's guide: This is one puzzle that really dislikes being mishandled. It took me at least 5 tries. This is how to do it: If you already have done anything to it, reset the puzzle. (Hint: You propably have to move the 4 sheets to the foreground, the one with the arrow pointing on with the short end to the left. You can also go back to puzzle menu to get the right view.) Now right click on the one sheet where the arrow from the text points to. Click tweak. Now click one time on the straight arrow to the right. Now the sheet should flip. use shake and wiggle it. That should raise your score to the needed points. Level 4.4 The Right Rotation Orange pointing in, blue pointing out. Right click a helix to Tweak it. Level 4.5 Changing the structure Changing the structure of the protein can help you see a solution better, and also affects Rebuild and Tweak. These three segments should be sheets. To enter Structure mode, click the Modes tab and choose Structure, or press 2. Right click a section of the protein while in structure mode to asign its structure from the three secondary structure types. Once you've done that, try using tweak to flip the sheet down. Use Shake and Wiggle to finish up. If the protein starts coming apart, you can use reset or undo. tip : click on pull mode, flip the sheet with the left arrow or rebuild the last part of the sheet. Game type Level 5-1 Quest to the native (QTTN) In this puzzle, the correct solution, called a NATIVE, is known. Use the tools available to match the protein with the guide. If you haven't discovered it yet, you can attach a rubber band from the protein to a point in empty space. Rubber bands also affect the pull tool, not just wiggle. Remember to freeze parts of the protein that you don't want warped by wiggle or pull. Level 5-2 Movin'along Sometimes you can MOVE whole pieces of the protein. Click on a piece to bring up the MOVE tool. Then press and hold down RIGHT BUTTON anywhere on the tool to drag the piece around. You can't pull on the backbone of this puzzle." Tip : Click on the helix, then on the purple star with the right button, then move the helix on the shadow, rotate the view to check then shake and wiggle. Level 5-3 Electron density In an Electron Density puzzle, we only have data on the rough shape of the protein. You are given this data as a 3D surface that predicts the general areas where parts of the protein are located. The backbone of the protein will fit neatly inside the 3D region, but it's up to you to work out how it fits. Click on the ELECTRON DENSITY button. These options let you control how the density surface is drawn. Adjust the THRESHOLD to change the thickness of the density region. At a good threshold, you can see shapes in the region that match parts of the protein. After moving the protein press ALIGN PROTEIN TO DENSITY to line up the surface with the protein. The alignment usually takes a few seconds to complete. Use Shake, Wiggle, and careful moving to fold the protein into the best possible shape that fits inside the predicted region. Tip : wiggle, shake, wiggle, shake, then drag the end of protein inside the cloud with caution, skahe, wiggle. Level 5-4 Exploration In exploration puzzles like this one, your goal is to find a solution that is different from the starting structure. Your calculated score will be the protein's base score times an exploration multiplier for finding new configurations. You can use the Contact Map to help you find new configurations for the protein. The rows and columns in Contact Map correspond to segments of the backbone. A black mark indicates that the segments corresponding to that row and column are in contact. The red areas are contacts present in the starting structure. White areas are new contacts, which increase your score multiplier. You can click on TUTORIAL to learn more about Exploration puzzles. Use all the tools you have learned to fold this protein into a new shape. Don't be afraid to break some connections to make new ones. Level 5-5 Control over crashing You may have noticed that using Wiggle when there are many clashes causes the protein to come apart. To avoid this, lower the CLASHING IMPORTANCE . This lets Wiggle keep making small adjustments even if the protein is packed too tight. A lower Clashing Importance also lets you make moves that add clashes without unravelling the protein, like pulling on a tangled strand. Try setting Clashing Importance to 0.1, then Wiggle while slowly increasing it. Sequences Level 5-1: Basic Threading These levels will introduce the powerful [[The Alignment Tool|'ALIGNMENT']] tool! It will let you use the structures of real proteins, called TEMPLATES, by THREADING. Click on the smiley button to bring up the ALIGNMENT tool. This 3D strcutures shows the backbone of the template. The bottom row of the letters is the TEMPLATE SEQUENCE. you can see it in 3D as spheres connected by lines. The top row of letters is the sequance of your protein. The cylinders in 3D show how its backbones lines up with the template. When you THREAD, your protein will try to fit onto the 3D template where the cylinders are. Click the little smiley to try threading. Now that you've threaded it, try a shake and wiggle! In this puzzle, you'll just need to use the ALIGNMENT tool to thread, then wiggle and shake. Don't worry about making manual adjustments. In this puzzle, you'll just need to use the ALIGNMENT tool to thread, then shake and wiggle. Level 5-2: Alignin' Sequences Bring up the alignment tool again. This time the letters and colors in the sequences are not lined up well.This middle row shows how well each letter matches; a bigger white bar means a better match. And this score (on the right) shows how the sequences match overall . You can click and drag or use the arrow keys to move the letters around. You can reset, undo, or redo with these buttons (on the left). Try to line up the colors. It's okay if there are spaces, but fewer spaces is better. Click here to thread when they match well! (the little smiley). Threading didn't work. Try to find a better match. Letters that blink red after trying to thread are causing problems. With a good alignment, you'll just need to use the ALIGNMENT tool to thread then wiggle and shake. Don't worry about making manual adjustments. With a good alignment, you'll just need to thread, shake, and wiggle. Level 5-3: A major shift The sequences don't always line up perfectly. You can look at the template structure to get an idea of what threading will do. A space in your sequence will stretch your protein when it is threaded. A space in the template sequence will squash your protein when it is threaded. Use the sequences to line this purple part up and make a good sheet; watch how the 3D structure moves when you change the aligment. But be careful how you align this loop! Look at the structure and keep any stretched segments away from the rest of the protein. If shake and wiggle doesn't work, try a different alignment! Threading didn't work. Put the only space after this letter! Letters that blink red after trying to thread are causing problems. Put the only space after this letter! tips : see the image, wait for the thread a long time, shake a long time and wiggle. Protein Design Level 6-1: Intro to Design Welcome to the design puzzles. In these challenges you will have the power to design new proteins! Segments with brighter colors can be designed! Some of these sidechains are too large. You can change them in Design Mode. To enter Design Mode, click the Modes tab and choose Design, or press 4. Select the segments you want to mutate. Click the Mutate Button from the menu. Then click the picture of the sidechain you want to mutate to Try to find better fits for both designable sidechains. If you're stuck, it may be easier to restart from the beginning. Level 6-2: Swapping Side Chains Now some sidechains are too small, causing voids! Try replacing them with some large ringed hydrophobics. You'll need to change to Design Mode. Level 6-3: Mass Mutate This helix has lot of unburied orange hydrophobics.You can change them to blue hydrophilics in Design Mode. Stop the Mutate Sidechains by pressing the space bar. You've earned a new tool! Mutate Sidechains is like Shake, but may mutate designable sidechains. Level 6-4: Insertion and Deletion ''' This red line is a CONSTRAINT, indicating that the segments it connects should be closer together. You can change the length of the helix by inserting or deleting segments. Right click a segment of the helix and use Insert Between. The blue blinking segments will show you where it will appear. The protein seems a little short now. You may want to undo or insert a segment. You can use wiggle and mutate sidechains to finish up. The protein seems a little long now. You may want to undo or delete a segment. More molecules '''Level 7-1 ligand debut These levels contain molecules other than proteins! This small molecule is a LIGAND. Proteins can be designed to bind ligands. Hydrogen bonds are important for binding ligands. Connect red atoms with blue atoms to form bonds between the ligand and sidechains! Left click on the ligand to bring up MOVE tool. RIGHT-button-drag to move left, right, up, and down, LEFT-button-drag to rotate and SHIFT-LEFT(or MIDDLE)-button-drag to move ligand Into/Out of screen. When the ligand is in a good place, try a wiggle! Level 7-2 Ligand constraints These are CONSTRAINTS. Red constraints are violated. Make the constraints become green! After moving the ligand closer, use WIGGLE SIDECHAINS to wiggle the sidechains and the ligand at the same time. Try and compare it to Shake Sidechains. Level 7-3: DNA Pairing Use Design Mode to find the correct match for the incorrectly paired sidechains. DNA sidechains pair according to color and size. Match sidechains of same color and opposite sizes to make lots of bonds! Level 7-4: DNA and Protein DNA can hydrogen bond to protein. Mutate the proteins to form better bonds.